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Biomedical subjects

James E Lynch

Publications and source records attributed to James E Lynch.

8 recordsLinked to original sources

Transthoracic closure of a postpneumonectomy bronchopleural fistula with coils and cyanoacrylate.

Standard treatment for persistent bronchopleural fistulas involves thoracotomy with primary closure and transposition of a vascularized muscle flap to the bronchial leak site. This major operation may be ineffective or medically contraindicated. We successfully treated 2 patients by insertion of coils and cyanoacrylate glue into and adjacent to the fistula of a postpneumonectomy bronchial stump with computed tomographic-guided transthoracic needle. The coils served as scaffolding for cyanoacrylate glue to control the bronchopleural fistula.

Adenocarcinoma↗

Mechanical ventilation and acute respiratory distress syndrome.

Acute respiratory distress syndrome continues to be a high-mortality condition. The role of mechanical ventilation remains primarily a supportive modality. Recent research has elucidated the adverse impact of traditional ventilation strategies on development of the disease and, ultimately, mortality. The institution of low tidal volume ventilation has been the only intervention that has resulted in definitive improvement in survival. Animal and human investigations that culminated in the Acute Respiratory Distress Syndrome Network low tidal volume study are reviewed. Current controversies in the application of mechanical ventilation including the use of positive end-expiratory pressure, recruitment maneuvers, and high frequency oscillatory ventilation are also addressed.

Animals↗

Adjuncts to mechanical ventilation in ARDS.

Since its first description, acute respiratory distress syndrome has been characterized by abnormal physiologic and gas exchange properties of the lungs. Many adjunctive therapies have been developed to reduce the stresses of mechanical ventilation on already damaged lungs. We examined the mechanism of action and the latest clinical trial information of several adjunctive therapies including prone positioning, nitric oxide, extracorporeal membrane oxygenation, arterial venous carbon dioxide removal, and liquid ventilation. While all of these therapies have demonstrated short-term improvements in arterial blood gases and in the limitation of lung injury, none have shown an evidence-based survival benefit.

Carbon Dioxide↗

Pertussis with severe pulmonary hypertension and leukocytosis treated with extracorporeal membrane oxygenation.

Pertussis, or "whooping cough," is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.

Extracorporeal Membrane Oxygenation↗

A survey for pain and sedation medications in pediatric patients during extracorporeal membrane oxygenation.

Routine administration of large amounts of pain and sedative medication is common to critically ill pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) for cardiopulmonary failure. It has been our experience that pediatric patients are the most difficult age group in which to achieve an ideal pain and sedative control due to the narrow margin of safety. The purpose of this study was to determine the general practice guideline used for pain and anxiolytic pharmacotherapy for pediatric patients at ECMO centers. We sent a survey questionnaire to all ECMO centers in the USA that treat pediatric respiratory failure patients. Of the 46 responding centers (including telephone follow-ups), 37 (80%) centers had an active pediatric ECMO programs for patients with severe respiratory failure. Fentanyl was the most commonly used pain medication and continuous infusion, administered directly to the patient, was preferred. Subjective effectiveness of various pharmacological agents was variable without clear consensus; however, midazolam was considered to be the most effective agent used.

Anesthetics↗

Production and purification of refolded recombinant human IL-7 from inclusion bodies.

A recombinant form of human rhIL-7 was overexpressed in Escherichia coli HMS174 (DE3) pLysS under the control of a T7 promoter. The resulting insoluble inclusion bodies were separated from cellular debris by cross-flow filtration and solubilized by homogenization with 6 M guanidine HCl. Attempts at refolding rhIL-7 from solubilized inclusion bodies without prior purification of monomeric, denatured rhIL-7 were not successful. Denatured, monomeric rhIL-7 was therefore initially purified by size-exclusion chromatography using Prep-Grade Pharmacia Superdex 200. Correctly folded rhIL-7 monomer was generated by statically refolding the denatured protein at a final protein concentration of 80-100 microg/ml in 100 mM Tris, 2mM EDTA, 500 mM L-arginine, pH 9.0, buffer with 0.55 g/l oxidized glutathione at 2-8 degrees C for at least 48 h. The refolded rhIL-7 was subsequently purified by low-pressure liquid chromatography, using a combination of hydrophobic interaction, cation-exchange, and size-exclusion chromatography. The purified final product was >95% pure by SDS-PAGE stained with Coomassie brilliant blue, high-pressure size-exclusion chromatography (SEC-HPLC), and reverse-phase HPLC. The endotoxin level was <0.05 EU/mg. The final purified product was biologically active in a validated IL-7 dependent pre-B-cell bioassay. In anticipation of human clinical trials, this material is currently being evaluated for safety and efficacy in non-human primate toxicology studies.

Electrophoresis, Polyacrylamide Gel↗

Percutaneous venovenous CO2 removal with regional anticoagulation in an ovine model.

Extracorporeal CO2 removal may reduce minute ventilation requirements and allow for better tolerance of low tidal volume ventilating strategies in patients with severe respiratory insufficiency. Conventional extracorporeal gas exchange is labor-intensive, expensive, and usually requires systemic anticoagulation. In this study, a simplified venovenous circuit was developed by using regional citrate anticoagulation to avoid potential complications associated with systemic heparin. Five healthy adult sheep underwent percutaneous placement of a double-lumen 18F catheter into the internal jugular vein. The extracorporeal circuit consisted of a hollow fiber oxygenator and a variable speed roller pump. Regional anticoagulation consisted of a continuous citrate infusion to the inflow limb of the circuit. Systemic calcium levels were maintained by calcium chloride infusion through a central line. CO2 transfer was measured at varying levels of blood and gas flow. CO2 transfer ranged from 31 ml/min (500 ml/min blood flow; 2 l/min gas flow) to 150 ml/min (1000 ml/min blood flow; 15 l/min gas flow) and was directly proportional to blood flow and gas flow (p < 0.05). Normocapnia was maintained despite a 75% reduction in minute ventilation. At 24 hours, there was no significant clot formation in the circuit.

Animals↗